2: Cells of Innate Immune System 🏁 Flashcards
APCs (types, task)
professional:
1. Dendritic Cell (viruses)
2. Macrophage (bacteria)
3. B cell (microbial toxins)
- nucleated cells (non professional)
- Granulocytes (atypical)
present endogenous and exogenous molecules to T cells via MHC
Antigen processing by APCs and pathways
endogenous proteins are processed in cytosol or secretory vesicles, presentation via MHCI to CD8+ T cell (MHC loading in ER, Transporter (TAP) needed)
MHCI presentation possible from all nucleated cells
exogenous proteins are processed in endosomes, presentation via MHCII to CD4+ T cell (MHC loading in endosome)
only from professional APCs
cross-presentation:
possible by specific DCs, presentation of exogenous proteins by MHCI
-> immune response against viruses, tumors and after vaccination
How does T cell stimulation work?
Immature DC in peripheral tissue -> PAMP recognition and activation -> maturation and migration to lymph node via CCR7 -> presentation to naive T cell in lymph node
How do granulocytes acquire APC-like function?
- de novo MHC-II synthesis possible upon stimulation by exogenous cytokines
- autocrine signalling
- neutrophils store MHC-II molecules intracellular
- receptor lead to cell cell contact to amplify differentiation into APCs
- basophils can acquire MHC-II from APCs via trogocytosis (MHC transfer)
Neutrophils (facts and development)
- 1-2 x 10^11 cells/day, maturation in bone marrow (10-15 d)
- no cell division, blood half-life of 4-10h
- first circulating cells that migrate to site of inflammation
primary granules:
myeloperoxidase (MPO), Elastase, Defensin
secondary granules:
Lactoferrin, Collagenase, Lysozyme
tertiary granules:
Gelatinise, Acetyltransferase
How do Neutrophils migrate to site of infection?
Extravasation
1. rolling on blood vessel endothelium via Selectin
2. tight binding to receptor via ICAM-1
3. diapedesis through endothelium via PECAM-1 and migration
What are the different functions of Neutrophils
Phagocytosis
Degranulation (antimicrobial)
APC-like character
NET formation (release of fibers)
ROS release
NK cells
- large granular lymphocytes
- natural cytotoxicity against virally infected and tumor cells
- belong to innate immune system (some have also memory-like function)
- produce cytokines (mainly IFN-y and TNF)
immature NK cell:
CD56 bright & CD16 dim
mature NK cell:
CD56 dim & CD16+++
(CD56 is only expressed on NK cells)
What are the effector functions of NK cells?
a. tolerance hypothesis:
recognition of MHC-I stops killing of healthy cell (even when presenting an antigen)
—> inhibition
b. missing self hypothesis:
loss/missing of MHC-I leads to killing of cell (tumor cells)
—> activation
c. stress induces self hypothesis:
stress induced ligands promote killing of cell
—> more activating signals then inhibitory once
How do NK cells induce the cytotoxicity?
- targeted release of lytic granules (perforin and granzyme)
- mediated via death receptor (TRAIL and FasL on NK TRAIL-R and Fas on target cell)
a. Cell-mediated cellular cytotoxicity
b. antibody-dependent cellular cytotoxicity (CD16 binds AB which is bound to target cell)
How does a Cytotoxicity assay work?
- co-culture of NK and target cells
a. tumor lysis leads to LDH release -> LDH release assay
b. activated NKs express CD107a on surface -> CD107a degranulation assay
Where do NK Cells matter?
- tumor immunosurveilance (when metastasising, not when established)
- clearance of virally infected cells
- clearance of senescent cells
- healthy pregnancy (CD56 superbright)-> also secret growth factors
B lymphocytes
B1a, B1b, B2 (marginal zone (15%)& follicular (70%)) & regB cells
development:
B1: fetal liver, then self renewal
B2: bone marrow & spleen (maturation)
What are the functions of B cells?
B-1a produce natural antibodies (nIgM)
- ABs are produced without prior antigen exposure
- paratope is germline encoded -> polyreactive and broadly unspecific
B1b have a T cell independent antigen response
secrete cytokines
